It has been proposed that interleukin-6 may play a role in the pathogenesis of autoimmune diseases like lupus erythematosus. We have therefore investigated the immunoreactivity of IL-6 in 32 skin biopsies of 23 patients suffering from chronic discoid lupus erythematosus (n = 16), subacute cutaneous lupus erythematosus (n = 5) and systemic lupus erythematosus (n = 5) as well as in uninvolved skin (n = 6) and in normal skin from healthy volunteers (n = 3). Increased immunohistochemical staining was detectable in 14 of 26 biopsies from lesional skin. The remaining biopsies from lesional, non-lesional and normal skin displayed only minimal or no reactivity, but 8 out of 12 lupus erythematosus patients had been pretreated with local or systemic antiinflammatory drugs. Irrespective of the LE subtype, immunolabelling was generally most intense in the basal layer of the epidermis, with additional intense suprabasal staining in sections from 2 of 5 SLE patients. Preferential production of IL-6 in the lower parts of the epidermis was confirmed by RNA in situ hybridization. No correlation was found between the deposition of immunoglobulins and complement at the dermo-epidermal junction and IL-6 expression in keratinocytes. These data suggest that IL-6 may be involved in LE although its exact role in the pathogenesis of the disease needs to be further elucidated.